Genome-Wide Association Study of Response to Selenium Supplementation and Circulating Selenium Concentrations in Adults of European Descent
Genome-Wide Association Study of Response to Selenium Supplementation and Circulating Selenium Concentrations in Adults of European Descent
复制标题
DOI：
10.1093/jn/nxaa355
复制
发表时间：
2021-02-01
影响因子：
4.2
通讯作者：
Jacobs, Elizabeth T.
中科院分区：
文献类型：
--
作者：
Batai, Ken;Trejo, Mario J.;Jacobs, Elizabeth T.
硒（Se）是一种微量元素，与许多健康状况有关。全基因组关联研究（GWAS）已经确定了血液和趾甲硒水平的变体，但没有GWAS已进行到目前为止对硒supplementation.Objectives的反应进行了GWAS确定的单核苷酸多态性（SNP）与硒浓度的变化后，1年的补充。在研究开始时进行基础血浆硒浓度的GWAS以评估硒应答的SNP是否与基础硒水平的SNP重叠。方法共有428名参与者，年龄在40-80岁之间，来自硒和塞来昔布试验（Sel/Cel试验），每天补充200 μ g硒化酵母，用于补充反应的GWAS。血浆硒浓度测定从血液样本收集时的招聘和1年后的补充。进行线性回归分析以评估每个SNP与Se浓度变化之间的关系。我们进一步研究是否确定的SNPs重叠与基础硒concentration.Results没有SNP显着相关的硒浓度的变化在全基因组的显着性水平。然而，位于NEK 6上游的rs 56856693在名义上与补充后硒浓度的变化相关（P = 4.41 × 10（-7）），另外两个SNP rs 11960388和rs6887869位于二甲基甘氨酸脱氢酶（DMGDH）/甜菜碱-同型半胱氨酸S-甲基转移酶（BHMT）区域（P = 0.01）。补充硒后，DMGDH/BHMT区域2个SNPs的等位基因与硒浓度的增加相关，也与基础硒浓度的增加密切相关（P = 8.67 × 10（-8））。结论来自Sel/Cel试验的欧洲血统参与者对硒补充反应的第一个GWAS表明，NEK 6和DMGDH/BHMT区域的SNPs影响对硒补充的反应。
Background Selenium (Se) is a trace element that has been linked to many health conditions. Genome-wide association studies (GWAS) have identified variants for blood and toenail Se levels, but no GWAS has been conducted to date on responses to Se supplementation.Objectives A GWAS was performed to identify the single nucleotide polymorphisms (SNPs) associated with changes in Se concentrations after 1 year of supplementation. A GWAS of basal plasma Se concentrations at study entry was conducted to evaluate whether SNPs for Se responses overlap with SNPs for basal Se levels. Methods A total of 428 participants aged 40-80 years of European descent from the Selenium and Celecoxib Trial (Sel/Cel Trial) who received daily supplementation with 200 mu g of selenized yeast were included for the GWAS of responses to supplementation. Plasma Se concentrations were measured from blood samples collected at the time of recruitment and after 1 year of supplementation. Linear regression analyses were performed to assess the relationship between each SNP and changes in Se concentrations. We further examined whether the identified SNPs overlapped with those related to basal Se concentrations.Results No SNP was significantly associated with changes in Se concentration at a genome-wide significance level. However, rs56856693, located upstream of the NEK6, was nominally associated with changes in Se concentrations after supplementation (P = 4.41 x 10(-7)), as were 2 additional SNPs, rs11960388 and rs6887869, located in the dimethylglycine dehydrogenase (DMGDH)/betaine-homocysteine S-methyltransferase (BHMT) region (P = 0.01). Alleles of 2 SNPs in the DMGDH/BHMT region associated with greater increases in Se concentrations after supplementation were also strongly associated with higher basal Se concentrations (P = 8.67 x 10(-8)).Conclusions This first GWAS of responses to Se supplementation in participants of European descent from the Sel/Cel Trial suggests that SNPs in the NEK6 and DMGDH/BHMT regions influence responses to supplementation.